title: OX40 costimulatory signals potentiate the memory commitment of effector CD8+ T cells.
abstract: A T cell costimulatory molecule, OX40, contributes to T cell expansion, survival, and cytokine production. Although several roles for OX40 in CD8(+) T cell responses to tumors and viral infection have been shown, the precise function of these signals in the generation of memory CD8(+) T cells remains to be elucidated. To address this, we examined the generation and maintenance of memory CD8(+) T cells during infection with Listeria monocytogenes in the presence and absence of OX40 signaling. We used the expression of killer cell lectin-like receptor G1 (KLRG1), a recently reported marker, to distinguish between short-lived effector and memory precursor effector T cells (MPECs). Although OX40 was dispensable for the generation of effector T cells in general, the lack of OX40 signals significantly reduced the number and proportion of KLRG1(low) MPECs, and, subsequently, markedly impaired the generation of memory CD8(+) T cells. Moreover, memory T cells that were generated in the absence of OX40 signals in a host animal did not show self-renewal in a second host, suggesting that OX40 is important for the maintenance of memory T cells. Additional experiments making use of an inhibitory mAb against the OX40 ligand demonstrated that OX40 signals are essential during priming, not only for the survival of KLRG1(low) MPECs, but also for their self-renewing ability, both of which contribute to the homeostasis of memory CD8(+) T cells.
authors.affiliation: Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Seyed Fazlollah
authors.initials: SF
authors.lastname: Mousavi
authors.forename: Pejman
authors.initials: P
authors.lastname: Soroosh
authors.forename: Takeshi
authors.initials: T
authors.lastname: Takahashi
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Yoshikai
authors.forename: Hao
authors.initials: H
authors.lastname: Shen
authors.forename: Leo
authors.initials: L
authors.lastname: Lefrançois
authors.forename: Jannie
authors.initials: J
authors.lastname: Borst
authors.forename: Kazuo
authors.initials: K
authors.lastname: Sugamura
authors.forename: Naoto
authors.initials: N
authors.lastname: Ishii
mesh_terms: D000208:Acute Disease; D000276:Adjuvants, Immunologic / Q000502:physiology*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D004195:Disease Models, Animal; D005260:Female; D007156:Immunologic Memory / Q000235:genetics; D037181:Lectins, C-Type / Q000037:antagonists & inhibitors / Q000502:physiology; D008089:Listeria monocytogenes / Q000235:genetics / Q000276:immunology; D008088:Listeriosis / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D053278:OX40 Ligand; D011971:Receptors, Immunologic; D053262:Receptors, OX40 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D013234:Stem Cells / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D015534:Trans-Activators / Q000037:antagonists & inhibitors / Q000502:physiology; D048069:Tumor Necrosis Factors / Q000172:deficiency / Q000235:genetics
chemical_list: D000276:Adjuvants, Immunologic; C113413:KLRG1 protein, human; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D053278:OX40 Ligand; D011971:Receptors, Immunologic; D053262:Receptors, OX40; C505717:Tnfrsf4 protein, mouse; C504586:Tnfsf4 protein, mouse; D015534:Trans-Activators; D048069:Tumor Necrosis Factors